Present address: ICORD (International Collaboration on Repair Discoveries), The University of British Columbia, Biosciences Building, 6270 University Blvd, Vancouver, BC, V6T 1Z4, Canada.
Glial cell line-derived neurotrophic factor increases calcitonin gene-related peptide immunoreactivity in sensory and motoneurons in vivo
Article first published online: 25 NOV 2003
European Journal of Neuroscience
Volume 18, Issue 10, pages 2713–2721, November 2003
How to Cite
Ramer, M. S., Bradbury, E. J., Michael, G. J., Lever, I. J. and McMahon, S. B. (2003), Glial cell line-derived neurotrophic factor increases calcitonin gene-related peptide immunoreactivity in sensory and motoneurons in vivo. European Journal of Neuroscience, 18: 2713–2721. doi: 10.1111/j.1460-9568.2003.03012.x
- Issue published online: 25 NOV 2003
- Article first published online: 25 NOV 2003
- Received 7 June 2003, revised 26 August 2003, accepted 11 September 2003
- dorsal root ganglion;
- spinal cord
Calcitonin gene-related peptide (CGRP) is expressed at high levels in roughly 50% of spinal sensory neurons and plays a role in peripheral vasodilation as well as nociceptive signalling in the spinal cord. Spinal motoneurons express low levels of CGRP; motoneuronal CGRP is thought to be involved in end-plate plasticity and to have trophic effects on target muscle cells. As both sensory and motoneurons express receptors for glial cell line-derived neurotrophic factor (GDNF) we sought to determine whether CGRP was regulated by GDNF. Rats were treated intrathecally for 1–3 weeks with recombinant human GDNF or nerve growth factor (NGF) (12 µg/day) and dorsal root ganglia and spinal cords were stained for CGRP. The GDNF treatment not only increased CGRP immunoreactivity in both sensory and motoneurons but also resulted in hypertrophy of both populations. By combined in situ hybridization and immunohistochemistry we found that, in the dorsal root ganglia, CGRP was up-regulated specifically in neurons expressing GDNF but not NGF receptors following GDNF treatment. Despite the increase in CGRP in GDNF-treated rats, there was no increase in thermal or mechanical pain sensitivity, while NGF-treated animals showed significant decreases in pain thresholds. In motoneurons, GDNF increased the overall intensity of CGRP immunoreactivity but did not increase the number of immunopositive cells. As GDNF has been shown to promote the regeneration of both sensory and motor axons, and as CGRP appears to be involved in motoneuronal plasticity, we reason that at least some of the regenerative effects of GDNF are mediated through CGRP up-regulation.